Z. A. Nevozinskaya(5, 6), candidate of medical Sciences, A. G. Soboleva(1), candidate of biological Sciences, E. A. Klimov(3, 4), doctor of biological Sciences, I. M. Korsunskaya(1, 6), doctor of medical Sciences, Professor, V. V. Sobolev(1, 2, 3), candidate of biological Sciences 1-Center of theoretical problems of physico-chemical pharmacology of RAS, 4 Kosygina str., Moscow, 119991, Russian Federation; 2-RESEARCH Institute of vaccines and sera. I. I. Mechnikov", RAMS, 5 Malyy Kazenny per., Moscow, 105064, Russian Federation; 3-LLC "University diagnostic laboratory», Russian Federation, 119331, Moscow, Vernadsky Ave., 29, POM. I; 4-MOSCOW state University. M. V. Lomonosov, faculty of biology, Russian Federation, 119234, Moscow, Leninskie Gory, 1, p. 12; 5-Russian national research medical UNIVERSITY University them. N. And. Pirogov" Ministry Of Health Of Russia, 1 Ostrovityanova str., Moscow, 117997, Russian Federation; 6GBUZ "Moscow scientific and practical center of dermatovenerology and cosmetology" DZM, 17, Leninsky prospect, Moscow, 119071, Russian Federation E-mail: [email protected]

The aim of the study was to investigate the expression of the MMP-1 gene in patients with a diagnosis of localized scleroderma. Methods. The study included 12 patients with an established diagnosis of localized scleroderma. The material of the study consisted of biopsies from the affected and uninfected areas of the skin. As a control in the work, biopsies of the same patients from unaffected areas of the skin were used. The analysis was carried out by real-time PCR. The statistical processing of the results was carried out by the 2-ΔΔCt method. Results. The values of the relative expression levels of the gene were obtained in all patients. Individual analysis of each patient showed the expression level of the MMP-1 gene in scleroderma affected skin to be lowered comparatively with the visually unaffected skin (control) in the range from 4.2 times to 20.8 times. The average value of the change in the expression level of the gene was reduced by 7.6±2.6 times. Patients were divided into two groups – with a limited plaque form and a common plaque form of scleroderma. In patients with a limited form of the disease, expression of the MMP-1 gene was shown to be significantly reduced by 5.3 times, and in patients with a common form of the disease it was reduced by 11-fold times. Conclusion. A quantitative measurement of the expression of the metalloproteinase-1 gene (MMP-1) by PCR-RT was performed. Experimentally there was showed a decrease in gene expression in scleroderma affected skin compared to unaffected skin.
scleroderma, gene expression, PCR-RT, MMP-1

Список литературы: 
  1. Gabrielli A., Avvedimento E.V., Krieg T. Scleroderma. The New England J. of medicine. 2009; 360 (19): 1989–2003.
  2. Jimenez S.A., Hitraya E., Varga J. Pathogenesis of scleroderma. Collagen Rheum Dis Clin. North Am. 1996; 22: 647–74.
  3. Lovell C.R., Nicholls A.C., Duance V.C., Bailey A.J. Characterization of dermal collagen in systemic sclerosis. Br. J. Dermatol. 1979; 100: 359–69.
  4. LeRoy E.C. Increased collagen synthesis by scleroderma skin fibroblasts in vitro: a possible defect in the regulation or activation of the scleroderma fibroblast. J. Clin. Invest. 1974; 54: 880–9.
  5. Sternlicht M.D., Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001; 17: 463–516.
  6. Eeckhout Y., Vaes G. Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. Biochem J. 1977; 166: 21–31.
  7. Apte S.S., Olsen B.R., Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family. J. Biol. Chem. 1995; 270: 14313–8.
  8. Sato S., Hayakawa I., Hasegawa M., Fujimoto M., Takehara K.. Function blocking autoantibodies against matrix metalloproteinase-1 in patients with systemic sclerosis. J. Invest Dermatol. 2003; 120: 542–7.
  9. Kulski J.K., Kenworthy W., Bellgard M., Taplin R., Okamoto K., Oka A., Mabuchi T., Ozawa A., Tamiya G., Inoko H. Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals. J. Mol. Med. 2005; 83 (12): 964–75.
  10. Sonkoly E., Wei T., Janson P.C., Saaf A., Lundeberg L., Tengvall-Linder M., Norstedt G., Alenius H., Homey B., Scheynius A. et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PloS one. 2007; 2 (7): 610.
  11. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif). 2001; 25 (4): 402–8.
  12. Kulski J.K., Kenworthy W., Bellgard M., Taplin R., Okamoto K., Oka A., Mabuchi T., Ozawa A., Tamiya G., Inoko H. Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals. J. of molecular medicine (Berlin, Germany). 2005; 83 (12): 964–75.
  13. Nagase H., Woessner J.F. Matrix metalloproteinases. J. Biol. Chem. 1999; 274: 21491–2.
  14. Hijova E. Matrix metalloproteinases: their biological function and clinical implications. Bratisl. Lek. Listy. 2005; 106 (3): 127–32.
  15. Hou P., Troen T., Ovejero M.C. et al. Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption. Bone. 2004; 34 (1): 37–47.
  16. Melerzanov A., Lavrov A., Sakania L., Korsunskaya I., Petersen E., Sobolev V. Effects of laser radiation on MMP gene expression in keratinocytes. PRIME. 2014; 4 (3): 38–45.
  17. Соболев В.В., Саутин М.Е., Свитич О.А., Лавров А.А., Корсунская И.М. Экспрессия гена MMP-12 при псориазе и атеросклерозе. Современные проблемы дерматовенерологии, иммунологии и врачебной косметологии. 2014; 30: 35–43.
  18. Соболев В.В., Соболева А.Г., Золотаренко А.Д., Саутин М.Е., Николаев А.А., Миннибаев М.Т., Потекаев Н.Н., Корсунская И.М., Брускин С.А. Экспрессия генов матриксных металлопротеаз в коже больных псориазом. Экспериментальная и клиническая дерматокосметология. 2013; 1: 56–9.
  19. Стародубцева Н.Л., Соболев В.В., Соболева А.Г., Николаев А.А., Брускин С.А. Экспрессия генов металлопротеаз (ММР-1, ММР-1, ММР-9, ММР-12) при псориазе. Генетика. 2011; 47 (9): 1254–61.
  20. Uitto J., Bauer E.A., Eisen A.Z. Scleroderma: increased biosynthesis of triple-helical type I and type III procollagens associated with unaltered expression of collagenase by skin fibroblasts in culture. The J. of clinical investigation. 1979; 64 (4): 921–30.
  21. Birdi N., Laxer R.M., Thorner P., Fritzler M.J., Silverman E.D. Localized scleroderma progressing to systemic disease. Case report and review of the literature. Arthritis and rheumatism. 1993; 36 (3): 410–5.